Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Clemencia Colmenares,   The Cleveland Clinic Foundation

Description
Mice homozygous for the targeted mutation die before or shortly after birth due to developmental defects. More than 80% of homozygotes on the 129 background exhibit exencephaly (severe neural tube closure defects) between embryonic day 15.5 (E15.5) and embryonic day 18.5 (E18.5). None exhibit facial clefting. The Donating Investigator reports that homozygotes display flattened or shorter snouts, iris malformation and polydactyly. The penetrance of the phenotype is highly background dependent. Heterozygotes are viable and fertile with timely cranial neural tube closure and, the Donating Investigator reports, no facial clefting. This mutant strain may be useful in studies of facial cleft formation, 1p36 deletion syndrome, oncogene function, apoptosis, and neural tube and skeletal muscle defects.

Development
A targeting vector containing a thymidine kinase-driven neomycin resistance cassette was used to disrupt exon 1 and generated a small deletion in the coding sequence. The construct was electroporated into 129P2/OlaHsd-derived E14.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric mice were bred to 129S6Tac (129P3) and then backcrossed to 129S6Tac for 18 generations before arriving at The Jackson Laboratory. After arriving, the mice were crossed to 129S1/SvlmJ once.

Control Information

	Control
	Wild-type from the colony
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Ski^tm1Cco allele

009092	A.129P-Skitm1Cco/J
005709	B6.129-Skitm1Cco/J

View Strains carrying   Ski^tm1Cco     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Shprintzen-Goldberg Craniosynostosis Syndrome; SGS   (SKI)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Ski^tm1Cco/Ski⁺

        involves: 129P2/OlaHsd * C57BL/6

• tumorigenesis
• increased incidence of chemically-induced tumors
  • n addition to the phenotype observed for heterozygotes on a 129P2 and Black Swiss background, heterozygotes on this background display increased succeptibility for tumors when injected IP with 9,10-dimethyl-1,2-benzanthracene   (MGI Ref ID J:73349)
• increased lymphoma incidence
  • the most frequent tumors to develop were malignant lymphomas   (MGI Ref ID J:73349)
• cellular phenotype
• increased cell proliferation
  • In addition to the phenotype observed for heterozygotes on a 129P2 and Black Swiss background, heterozygotes on this background display increased rate of proliferation for MEF in culture   (MGI Ref ID J:73349)
• homeostasis/metabolism phenotype
• increased incidence of chemically-induced tumors
  • n addition to the phenotype observed for heterozygotes on a 129P2 and Black Swiss background, heterozygotes on this background display increased succeptibility for tumors when injected IP with 9,10-dimethyl-1,2-benzanthracene   (MGI Ref ID J:73349)

Ski^tm1Cco/Ski⁺

        involves: 129P2/OlaHsd * Black Swiss

• craniofacial phenotype
• midline facial cleft
  • frontonasal clefting occasionally seen   (MGI Ref ID J:42573)
• nervous system phenotype
• abnormal neural tube morphology/development   (MGI Ref ID J:42573)
• exencephaly
  • occasional exencephally seen   (MGI Ref ID J:42573)
• embryogenesis phenotype
• abnormal neural tube morphology/development   (MGI Ref ID J:42573)

Ski^tm1Cco/Ski^tm1Cco

        involves: 129P2/OlaHsd * C57BL/6

• mortality/aging
• partial lethality throughout fetal growth and development
  • while the phenotype expressed on this background is essentially the same as that on a 129P2 and Black Swiss background, embryonic lethality was delayed to between E14.5 and E18.5 while the phenotype expressed on this background is essentially the same as that on a 129P2 and Black Swiss background, embryonic lethality was delayed to between E14.5 and E18.5   (MGI Ref ID J:42573)
• craniofacial phenotype
• midline facial cleft
  • While the phenotype expressed on this background is essentially the same as that on a 129P2 and Black Swiss background, as backcrossing to C57BL/6 continues the frequency of facial clefts increases   (MGI Ref ID J:75396)
• muscle phenotype
• muscle hypoplasia
  • While the phenotype expressed on this background is essentially the same as that on a 129P2 and Black Swiss background, on a C57BL/6 background 50-60% of homozygous mice were obviously skinny with flaccid limbs   (MGI Ref ID J:42573)
• nervous system phenotype
• exencephaly
  • While the phenotype expressed on this background is essentially the same as that on a 129P2 and Black Swiss background, continued backcrossing to C57BL/6 reduces frequency of exencephaly   (MGI Ref ID J:75396)

Ski^tm1Cco/Ski^tm1Cco

        involves: 129P2/OlaHsd * Black Swiss

• mortality/aging
• complete perinatal lethality
  • homozygotes dead at birth   (MGI Ref ID J:42573)
  • E18.5 pups born live by cesarean died shortly after birth   (MGI Ref ID J:42573)
• partial lethality throughout fetal growth and development
  • moderate   (MGI Ref ID J:42573)
  • occurs between E9.5 and E14.5   (MGI Ref ID J:42573)
• cardiovascular system phenotype
• hemorrhage
  • in E18.5 embryos delivered by cesarean, severe hemorrhage occurs from exposed brain mass   (MGI Ref ID J:42573)
• cellular phenotype
• increased cell proliferation
  • increased rate of proliferation for MEF in culture   (MGI Ref ID J:73349)
• craniofacial phenotype
• abnormal jaw morphology
  • abnormal square jaw   (MGI Ref ID J:42573)
• • short mandible
    • mandibular bone is short and thick   (MGI Ref ID J:42573)
• abnormal neurocranium morphology   (MGI Ref ID J:42573)
• • abnormal presphenoid bone morphology
    • presphenoid is always absent or abnormal   (MGI Ref ID J:42573)
  • absent frontal bone
    • loss of frontal bones   (MGI Ref ID J:42573)
  • absent interparietal bone
    • loss of interparietal bones   (MGI Ref ID J:42573)
  • absent parietal bone
    • loss of parietal bones   (MGI Ref ID J:42573)
  • small basioccipital bone
    • basioccipital bones are small and malformed   (MGI Ref ID J:42573)
  • small basisphenoid bone
    • basisphenoid is small and malformed   (MGI Ref ID J:42573)
• midline facial cleft
  • frontonasal clefting found in 15% of pups and E18.5 embryos   (MGI Ref ID J:42573)
• shortened head
  • facial flattening   (MGI Ref ID J:42573)
• embryogenesis phenotype
• abnormal mesenchyme morphology
  • excessive apoptosis in craniofacial mesenchyme at E9.5 but not E10.5   (MGI Ref ID J:42573)
  • mesenchyme adjacent to neural tube was somewhat disorganized   (MGI Ref ID J:42573)
• open neural tube
  • defect at the level of the midbrain-forebrain boundary and extending forward and backward or in one or the other direction   (MGI Ref ID J:42573)
  • occurs in about 85% of embryos   (MGI Ref ID J:42573)
  • excessive apoptosis at E9.5 but not at E10.5   (MGI Ref ID J:42573)
  • no caudal neural tube defects, spina bifida or kinky tails   (MGI Ref ID J:42573)
• growth/size phenotype
• decreased fetal size
  • E18.5 pups delivered by cesarean were 10% smaller than normal   (MGI Ref ID J:42573)
• limbs/digits/tail phenotype
• polydactyly
  • vestigial hexadactyly   (MGI Ref ID J:75396)
• muscle phenotype
• abnormal skeletal muscle morphology
  • increased space between muscle fibers   (MGI Ref ID J:42573)
• • abnormal skeletal muscle fiber morphology
    • fibers were shorter and somewhat disorganized   (MGI Ref ID J:42573)
  • • decreased skeletal muscle fiber diameter
      • reduced diameter of muscle fibers   (MGI Ref ID J:42573)
  • decreased skeletal muscle mass   (MGI Ref ID J:42573)
• muscle hypoplasia
  • on a Swiss Black background, 15% extremely emaciated and 20% somewhat skinny   (MGI Ref ID J:42573)
• skeleton phenotype
• abnormal cervical vertebrae morphology
  • first three cervical vertebrae affected   (MGI Ref ID J:42573)
• • abnormal cervical atlas morphology   (MGI Ref ID J:42573)
  • abnormal cervical axis morphology   (MGI Ref ID J:42573)
• abnormal jaw morphology
  • abnormal square jaw   (MGI Ref ID J:42573)
• • short mandible
    • mandibular bone is short and thick   (MGI Ref ID J:42573)
• abnormal neurocranium morphology   (MGI Ref ID J:42573)
• • abnormal presphenoid bone morphology
    • presphenoid is always absent or abnormal   (MGI Ref ID J:42573)
  • absent frontal bone
    • loss of frontal bones   (MGI Ref ID J:42573)
  • absent interparietal bone
    • loss of interparietal bones   (MGI Ref ID J:42573)
  • absent parietal bone
    • loss of parietal bones   (MGI Ref ID J:42573)
  • small basioccipital bone
    • basioccipital bones are small and malformed   (MGI Ref ID J:42573)
  • small basisphenoid bone
    • basisphenoid is small and malformed   (MGI Ref ID J:42573)
• abnormal skeleton development   (MGI Ref ID J:75396)
• abnormal spine curvature
  • abnormal curvature of the back, head and neck   (MGI Ref ID J:42573)
• vertebral transformation
  • homeotic transformations unless facial clefting is present   (MGI Ref ID J:42573)
• vision/eye phenotype
• eyelids open at birth
  • homozygotes are born with their eyes open   (MGI Ref ID J:42573)
• nervous system phenotype
• abnormal forebrain morphology
  • ventral midline fusion of the forebrain   (MGI Ref ID J:75396)
• • abnormal olfactory bulb morphology
    • malformed olfactory bulb   (MGI Ref ID J:75396)
• exencephaly
  • exposed brain mass normally sheared off in normal birth   (MGI Ref ID J:42573)
• open neural tube
  • defect at the level of the midbrain-forebrain boundary and extending forward and backward or in one or the other direction   (MGI Ref ID J:42573)
  • occurs in about 85% of embryos   (MGI Ref ID J:42573)
  • excessive apoptosis at E9.5 but not at E10.5   (MGI Ref ID J:42573)
  • no caudal neural tube defects, spina bifida or kinky tails   (MGI Ref ID J:42573)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Developmental Biology Research
Craniofacial and Palate Defects
      cleft palate and cleft lip
      congenital cleft palate
Eye Defects
Neural Tube Defects
Perinatal Lethality
      Homozygous
Skeletal Defects
      polydactyly

Neurobiology Research
Neural Tube Defects

Sensorineural Research
Eye Defects
Olfactory Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Skitm1Cco
Allele Name		targeted mutation 1, Clemencia Colmenares
Allele Type		Targeted (knock-out)
Common Name(s)		ski-;
Mutation Made By		Clemencia Colmenares,   The Cleveland Clinic Foundation
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14.1
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Ski, ski sarcoma viral oncogene homolog (avian)
Chromosome		4
Gene Common Name(s)		2310012I02Rik; 2610001A11Rik; AA062172; AA589460; BC004088; MGC:8300; RIKEN cDNA 2310012I02 gene; RIKEN cDNA 2610001A11 gene; SGS; SKV; cDNA sequence BC004088; expressed sequence AA062172; expressed sequence AA589460;
Molecular Note		Insertion of a neomycin resistance cassette into the exon 1 generated a small deletion in the coding sequence. [MGI Ref ID J:42573]

Genotyping

Genotyping Information

Genotyping Protocols

Ski^tm1Cco, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Berk M; Desai SY; Heyman HC; Colmenares C. 1997. Mice lacking the ski proto-oncogene have defects in neurulation, craniofacial, patterning, and skeletal muscle development. Genes Dev 11(16):2029-39. [PubMed: 9284043]  [MGI Ref ID J:42573]

Additional References

Ski^tm1Cco related

Atanasoski S; Notterpek L; Lee HY; Castagner F; Young P; Ehrengruber MU; Meijer D; Sommer L; Stavnezer E; Colmenares C; Suter U. 2004. The protooncogene Ski controls Schwann cell proliferation and myelination. Neuron 43(4):499-511. [PubMed: 15312649]  [MGI Ref ID J:96530]

Baranek C; Dittrich M; Parthasarathy S; Bonnon CG; Britanova O; Lanshakov D; Boukhtouche F; Sommer JE; Colmenares C; Tarabykin V; Atanasoski S. 2012. Protooncogene Ski cooperates with the chromatin-remodeling factor Satb2 in specifying callosal neurons. Proc Natl Acad Sci U S A 109(9):3546-51. [PubMed: 22334647]  [MGI Ref ID J:182157]

Colmenares C; Heilstedt HA; Shaffer LG; Schwartz S; Berk M; Murray JC; Stavnezer E. 2002. Loss of the SKI proto-oncogene in individuals affected with 1p36 deletion syndrome is predicted by strain-dependent defects in Ski-/- mice. Nat Genet 30(1):106-9. [PubMed: 11731796]  [MGI Ref ID J:75396]

Dai P; Shinagawa T; Nomura T; Harada J; Kaul SC; Wadhwa R; Khan MM; Akimaru H; Sasaki H; Colmenares C; Ishii S. 2002. Ski is involved in transcriptional regulation by the repressor and full-length forms of Gli3. Genes Dev 16(22):2843-8. [PubMed: 12435627]  [MGI Ref ID J:80205]

Ernest S; Christensen B; Gilfix BM; Mamer OA; Hosack A; Rodier M; Colmenares C; McGrath J; Bale A; Balling R; Sankoff D; Rosenblatt DS; Nadeau JH. 2002. Genetic and molecular control of folate-homocysteine metabolism in mutant mice. Mamm Genome 13(5):259-67. [PubMed: 12016514]  [MGI Ref ID J:76559]

McGannon P; Miyazaki Y; Gupta PC; Traboulsi EI; Colmenares C. 2006. Ocular abnormalities in mice lacking the Ski proto-oncogene. Invest Ophthalmol Vis Sci 47(10):4231-7. [PubMed: 17003410]  [MGI Ref ID J:116273]

Nomura T; Khan MM; Kaul SC; Dong HD; Wadhwa R; Colmenares C; Kohno I; Ishii S. 1999. Ski is a component of the histone deacetylase complex required for transcriptional repression by Mad and thyroid hormone receptor. Genes Dev 13(4):412-23. [PubMed: 10049357]  [MGI Ref ID J:53313]

Shinagawa T; Nomura T; Colmenares C; Ohira M; Nakagawara A; Ishii S. 2001. Increased susceptibility to tumorigenesis of ski-deficient heterozygous mice. Oncogene 20(56):8100-8. [PubMed: 11781823]  [MGI Ref ID J:73349]

Tesseur I; Wyss-Coray T. 2006. A role for TGF-beta signaling in neurodegeneration: evidence from genetically engineered models. Curr Alzheimer Res 3(5):505-13. [PubMed: 17168649]  [MGI Ref ID J:125213]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes die before or shortly after birth.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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